Monocular Enucleation Research Articles

Alteration of Visual Input Results in a Coordinated Reorganization of Multiple Visual Cortex Maps

In the adult visual cortex, multiple feature maps exist and have characteristic spatial relationships with one another. The relationships can be reproduced by "dimension-reduction" computational models, suggesting that the principles of continuity and coverage may underlie cortical map organization. However, the mechanisms responsible for establishing these relationships are unknown. We explored whether removing one feature map during development causes a coordinated reorganization of the remaining maps or whether the remaining maps are unaffected. We removed the ocular dominance map by monocular enucleation in newborn ferrets, so that single eye stimulation drove the cortex in a more spatially uniform manner in adult monocular animals compared with normal animals. Maps of orientation, spatial frequency, and retinotopy formed in monocular ferrets, but their structures and spatial relationships differed from those in normal ferrets. The wavelength of the orientation map increased, so that the average orientation gradient across the cortex decreased. The decrease in the orientation gradient in monocular animals was most prominent in the high gradient regions of the spatial frequency map, indicating a coordinated reorganization between these two maps. In monocular animals, the orthogonal relationship between the orientation and spatial frequency maps was preserved, and the orthogonal relationship between the orientation and retinotopic maps became more pronounced. These results were consistent with detailed predictions of a dimension-reduction model of cortical organization. Thus, the number of feature maps in a cortical area influences the relationships between them, and inputs to the cortex have a significant role in generating these relationships.

History of ophthalmology: a distinguished or extinguished field of scholarly activity?

‘If I have seen further [than certain other men], it is by standing upon the shoulders of giants.’ (Isaac Newton, letter to Robert Hook, February 5th, 1675) Acta Ophthalmologica Scandinavica is one of the few international, peer-reviewed ophthalmology journals to publish papers dealing with the history of ophthalmology. In an analysis of papers on the history of ophthalmology published in Acta in the years 1998–2006, six articles were found, representing less than one per year. These were: (1) ‘Danish Ophthalmology from 1950 to 1975’ (Ehlers 2002); (2) ‘Gustav Østerberg in the footsteps of Hans Christian Andersen’ (Mellemgaard 2002); (3) ‘The history of the Ophthalmological Society of Copenhagen’ (Andersen 2002); (4) ‘The Society’s archives' (Norn 2002); (5) ‘Marius Tscherning (1854−1939):his life and work in optical physiology’ (Norn & Jensen 2004), and (6) ‘Jesus and the eye: New Testament miracles of vision’ (Mansour et al. 2005). An analysis of presentations at the two major European conferences gave similar results. The Nordic Congress of Ophthalmology (NOK) 2006 included a session on the history of ophthalmology, at which six papers were presented: (1) ‘Horner’s syndrome – eponymic confusion and conflict of contriver' (Havelius 2006); (2) ‘The great confusion and the Karolinska Institute in Stockholm 1888–1892’ (Tengroth 2006); (3) ‘A Swedish rural hospital 1886–1903’ (Ehinger 2006); (4) ‘Evil eyes’ (Mellemgaard 2006); (5) ‘Bjerrum’s glaucoma theory in 1889' (Norn 2006), and (6) ‘Tobacco amblyopia – historical overview of 200 years of the subject’ (Grzybowski 2006). Meanwhile, at the 2006 Meeting of the European Association of Vision and Eye Research (EVER), only one paper was presented at the free papers session: ‘Edmonde Mariotte (1620–1684), pioneer of neurophysiology and neuro-ophthalmology’ (Grzybowski & Aydin 2006). However, the General Assembly of EVER, following my formal proposal, has decided to open a subsection for the history of ophthalmology in the hope that more papers will be submitted and a full section might be established in the future. The reason for such scant interest in the history of ophthalmology might be related to the fact that it is perceived as a field of science in which there is almost no possibility of further development and in which nothing of interest can any longer be discovered. Some even claim that everything in the history of ophthalmology has already been described. As an illustration of how present knowledge has its origins in the past and of how many erroneous opinions should be reconsidered, let us examine the case of Wilbrand's knee. As is well known, Wilbrand's knee is part of the optic nerve. It appears in the majority of contemporary textbooks of ophthalmology and neuro-ophthalmology, and damage to it was previously assumed to be responsible for junctional scotoma. However, 10 years ago, Horton demonstrated that Wilbrand's knee is an artefact of monocular enucleation and proposed that anterior chiasmal syndrome has a limited localizing value (Horton 1997). Why the history of ophthalmology should undergo continual re-examination is further illustrated by the fact that many papers on ophthalmology are published in the native language of their authors and are neither translated into other languages nor presented internationally. At NOK 2006 this problem was nicely exemplified by Mogens Norn, in his work on Bjerrum's glaucoma theory. There are at least two other reasons why we should study the history of ophthalmology, apart from mere scholarly interests. Firstly, it demonstrates respect for our predecessors, tutors and masters of ophthalmology, whose lives and work deserve to be described and remembered. Secondly − and this is probably more important for general ophthalmology journals such as Acta, and conferences such as those held by NOK and EVER − the history of our discipline from ancient times to the present day imbues us with the conviction that, to paraphrase Harry Moss Traquair's statement that ‘perimetry is done by perimetrist not, perimeter’, ‘ophthalmology is performed by the ophthalmologist, not by the ophthalmic equipment’. In conclusion, I believe there is ample room for research in the history of ophthalmology, both at the national and international level. Much of this could be presented at EVER 2007 (the deadline for submissions to its newly established subsection is June 1st, 2007) or at NOK 2008 (which already has a history of ophthalmology section!).

Dynamic changes in CREB phosphorylation and neuroadaptive gene expression in area V1 of adult monkeys after monocular enucleation

Our understanding of the molecular events that emerge after change in sensory input remains elusive, especially with regard to mature area V1. Here, we characterized P-CREB expression in area V1 of monkeys at multiple time-points after monocular enucleation (ME) to assess the possible contribution of CREB in visually deprived neocortex. Immunoblot assays and immunostainings showed that P-CREB is dynamically regulated in adult area V1, reaching a peak level between 5 and 30 days after ME, and becoming reduced at the 90-day post-ME time-point. This striking temporal increase in P-CREB level was paralleled by a concomitant increase of two CREB-regulated pro-survival effectors, namely Bcl-2 and Bcl-w. We present our results in the context of recent advances about adult visual neocortex and propose that ME induces a multifaceted CREB-mediated response that favors intrinsic stability of neurons and facilitates mature cortical networks to reorganize over a prolonged period.

Development and plasticity of the retina in the opossum Monodelphis domestica

We investigated the rate of cell proliferation and death in the retina of the Monodelphis opossum during its postnatal development and the influence of early monocular enucleation on these processes. Our results show that in the opossum, as in other marsupials, the peak of the retinal cells divisions occurs postnatally and that generation of retinal cells continues till the time of eye opening (P34), except of the marginal rim, where it continued till P60. Ganglion and amacrine cells are generated between postnatal days (P) P4 and P9, while bipolar cells and photoreceptors are generated simultaneously between P14 and P25. The peak of ganglion cell death as detected by the TUNEL method occurs around P14-19 in the center of retina. The second peak of apoptosis appears in the inner nuclear layer (INL) at P19-25. Gliogenesis takes place between P25 and P34. We also found that monocular enucleation performed during the early period of retinal development (P0-P7) did not influence proliferation, developmental apoptosis or other developmental processes in the retina of the remaining eye.

Differential regulation of the neuronal isoform of nitric oxide synthase in the superior colliculus and dorsal lateral geniculate nucleus of the adult rat brain following eye enucleation

Nitric oxide has been shown to play various physiological and pathological roles in the visual system. We studied here the expression of the neuronal isoform of nitric oxide synthase in the rat superior colliculus and in the dorsal lateral geniculate nucleus after unilateral enucleation, by means of immunohistochemistry, immunoblotting, and real-time PCR. Immunohistochemistry revealed an increase of nitric oxide synthase-positive neurons in specific layers of the superior colliculus and in the dorsal lateral geniculate nucleus between 1 and 30 days post-lesion. Immunoblotting analyses confirmed that the neuronal isoform of nitric oxide synthase is upregulated in the superior colliculus and in the dorsal lateral geniculate nucleus after retinal removal. Diaminofluorescein histochemistry suggested that nitric oxide production was increased in both deafferented retinorecipient areas. Our real-time PCR results indicated that nitric oxide synthase transcript levels in the superior colliculus were not significantly altered after monocular enucleation, although an upregulation of the enzyme transcription was detected into the deafferented dorsal lateral geniculate nucleus. These findings indicated that neuronal nitric oxide synthase may undergo different forms of regulation in the adult deafferented visual system.

Cytochrome Oxidase and Neurofilament Reactivity in Monocularly Deprived Human Primary Visual Cortex

Previous studies of human primary visual cortex (V1) have demonstrated a significant eye-specific decrease in cytochrome oxidase (CO) staining following monocular enucleation. We have extended these results by examining CO staining and neurofilament labeling in V1 from a patient with long-standing monocular blindness. A pattern of reduced neurofilament reactivity was found to align with pale CO-stained ocular dominance columns. Neurons located within deprived ocular dominance columns were significantly smaller compared with those in nondeprived columns. A spatial analysis of the relationship between CO blobs and ocular dominance columns revealed that both deprived and nondeprived blobs tended to align with the centers of ocular dominance columns.

Central projections of melanopsin‐expressing retinal ganglion cells in the mouse

A rare type of ganglion cell in mammalian retina is directly photosensitive. These novel retinal photoreceptors express the photopigment melanopsin. They send axons directly to the suprachiasmatic nucleus (SCN), intergeniculate leaflet (IGL), and olivary pretectal nucleus (OPN), thereby contributing to photic synchronization of circadian rhythms and the pupillary light reflex. Here, we sought to characterize more fully the projections of these cells to the brain. By targeting tau-lacZ to the melanopsin gene locus in mice, ganglion cells that would normally express melanopsin were induced to express, instead, the marker enzyme beta-galactosidase. Their axons were visualized by X-gal histochemistry or anti-beta-galactosidase immunofluorescence. Established targets were confirmed, including the SCN, IGL, OPN, ventral division of the lateral geniculate nucleus (LGv), and preoptic area, but the overall projections were more widespread than previously recognized. Targets included the lateral nucleus, peri-supraoptic nucleus, and subparaventricular zone of the hypothalamus, medial amygdala, margin of the lateral habenula, posterior limitans nucleus, superior colliculus, and periaqueductal gray. There were also weak projections to the margins of the dorsal lateral geniculate nucleus. Co-staining with the cholera toxin B subunit to label all retinal afferents showed that melanopsin ganglion cells provide most of the retinal input to the SCN, IGL, and lateral habenula and much of that to the OPN, but that other ganglion cells do contribute at least some retinal input to these targets. Staining patterns after monocular enucleation revealed that the projections of these cells are overwhelmingly crossed except for the projection to the SCN, which is bilaterally symmetrical.

Bigenomic functional regulation of all 13 cytochrome c oxidase subunit transcripts in rat neurons in vitro and in vivo

Cytochrome c oxidase is a multisubunit, bigenomically encoded inner mitochondrial membrane protein. Its enzymatic activity and amount in the brain vary with metabolic demands, but the precise regulation of all 13 subunits to form a functional holoenzyme in a 1:1 stoichiometry is not well understood. To determine if all 13 subunit transcripts were coordinately regulated by functional alteration in neurons, cultured primary neurons were depolarized by potassium chloride for 5–24 h, or tetrodotoxin inactivated for 2–6 days. In vivo studies were done on rats monocularly enucleated for 4 days to 2 weeks. Expressions of cytochrome c oxidase subunit mRNAs were measured by real-time quantitative polymerase chain reaction. Results showed that in vitro, all 13 transcripts were significantly up-regulated after 5 h of depolarizing stimulation. With tetrodotoxin blockade, however, the three mitochondrial-encoded transcripts were down-regulated earlier than the 10 nuclear ones (2 days versus 4 days). In vivo, all three mitochondrial-encoded subunit mRNAs were also down-regulated earlier than the nuclear ones in deprived visual cortex (4 days versus 1 week after monocular enucleation). Cytochrome c oxidase activity and protein levels were significantly decreased in parallel after 4 days of deprivation in vitro and 1 week in vivo. Our results are consistent with a coordinated mechanism of up-regulation of all 13 transcripts in response to functional stimulation, but an earlier and more severe down-regulation of the mitochondrial transcripts than the nuclear ones in response to functional deprivation. Thus, the mitochondrial subunits may play a more important role in regulating cytochrome c oxidase protein amount and activity in neurons. Our results also point to the need of all 13 subunits to form a functional holoenzyme.

Calcium-binding Protein Calretinin Immunoreactivity in the Dog Superior Colliculus

We studied calretinin-immunoreactive (IR) fibers and cells in the canine superior colliculus (SC) and studied the distribution and effect of enucleation on the distribution of this protein. Localization of calretinin was immunocytochemically observed. A dense plexus of anti-­calretinin-IR fibers was found within the upper part of the superficial gray layer (SGL). Almost all of the labeled fibers were small in diameter with few varicosities. The intermediate and deep layers contained many calretinin-IR neurons. Labeled neurons within the intermediate gray layer (IGL) formed clusters in many sections. By contrast, labeled neurons in the deep gray layer (DGL) did not form clusters. Calretinin-IR neurons in the IGL and DGL varied in morphology and included round/oval, vertical fusiform, stellate, and horizontal neurons. Neurons with varicose dendrites were also labeled in the IGL. Most of the labeled neurons were small to medium in size. Monocular enucleation produced an almost complete reduction of calretinin-IR fibers in the SC contralateral to the enucleation. However, many calretinin-IR cells appeared in the contralateral superficial SC. Enucleation appeared to have no effect on the distribution of calretinin-IR neurons in the contralateral intermediate and deep layers of the SC. The calretinin-IR neurons in the superficial dog SC were heterogeneous small- to medium-sized neurons including round/oval, vertical fusiform, stellate, pyriform, and ­horizontal in shape. Two-color immunofluorescence revealed that no cells in the dog SC ­expressed both calretinin and GABA. Many horseradish peroxidase (HRP)-labeled retinal ganglion cells were seen after injections into the superficial layers. The vast majority of the double-labeled cells (HRP and calretinin) were small cells. The present results indicate that antibody to calretinin labels subpopulations of neurons in the dog SC, which do not express GABA. The results also suggest that the calretinin-IR afferents in the superficial layers of the dog SC originate from small class retinal ganglion cells. The expression of calretinin might be changed by the cellular activity of selective superficial collicular neurons. These results are valuable in delineating the basic neurochemical architecture of the dog visual system.

Changes of parvalbumin immunoreactive neurons and GFAP immunoreactive astrocytes in the rat lateral geniculate nucleus following monocular enucleation

The expression of calcium binding proteins (CaBPs) has been linked to protection of neurons. The present study investigated the effects of monocular enucleation on the distribution of parvalbumin immunoreactive (PV-IR) neurons and glial fibrillary acidic protein immunoreactive (GFAP-IR) astrocytes in both the dorsal (dLGN) and ventral (vLGN) regions of the lateral geniculate nucleus (LGN). Our results demonstrated an increase in PV-IR neuronal density on the contralateral vLGN at 1-week post-enucleation (PE), which was maintained without significant change for 12 weeks. By contrast, PV-IR neurons in dLGN decreased significantly at all time point examined. The number of GFAP-IR astrocytes showed an initial increase from 1 to 4 weeks PE and then gradually decreased until 48 weeks in both regions of the LGN with contralateral side predominance. The present results suggest that monocular enucleation results in variable expression of PV-IR neurons and GFAP-IR astrocytes in the LGN complex, which may play an important role in neuronal degeneration and neuroplasticity of the rat visual system.

Glucose Metabolism in the Visual Structures of Rat Monocularly Deprived by Eyelid Suture after Postnatal Eye Opening

To determine the changes in the visual centers of rats following monocular visual deprivation after postnatal eyelid opening (PEO). Monocular eyelid suture was performed on rats on days 1, 3, 5, 7, 14, and 28 after PEO, and the glucose metabolism was measured 1, 2, 5, and 7 days after the eyelid suture. Ex vivo autoradiography with (14)C- or (18)F-labeled 2-deoxy-D-glucose was carried out. Effects of monocular enucleation or dark rearing were also determined. Monocular eyelid suture did not decrease the glucose metabolism in any contralateral visual structures on day 1 after visual deprivation in the PEO1 or PEO3 lid-sutured rats. However, there was a decrease on day 1 after the eyelid suture in PEO7 and older rats. Similarly, monocular enucleation on PEO1 did not reduce the glucose metabolism in the visual cortex (VC), but enucleation on PEO7 and thereafter did. Eyelid suture on PEO8 following dark rearing until PEO7 did not reduce the glucose metabolism 1 day after suture, but reduced it at 7 days after suture. Glucose metabolism was altered by visual deprivation on PEO7 and thereafter. Five days of visual experience after PEO were required for initiation of visual function in the rat visual system.

Effects of Monocular Enucleation on Calbindin-D 28k and c-Fos Expression in the Lateral Geniculate Nucleus in Rats

The present study was undertaken to evaluate the effects of monocular enucleation on the calbindin-D 28k (CB) and c-Fos immunoreactive (IR) neurons in the lateral geniculate nucleus (LGN) complex of adult rats. The enucleation resulted in neuronal degeneration and decrease of neurons in the LGN complex. Our study demonstrated a decrease of CB-IR neuronal density on the contralateral side of the ventral (vLGN) and dorsal LGN (dLGN) until 12 weeks post-enucleation (PE). On the ipsilateral side, CB-IR neuronal density in the dLGN and vLGN showed significant and continuous decrease until 48 and 12 weeks PE, respectively. In an additional experiment, c-Fos-IR neurons were increased at 2 days PE in the vLGN with ipsilateral predominance. At 7 days, c-Fos-IR neurons on the ipsilateral vLGN were still higher than those of pre-enucleated rats. The present results suggest that monocular enucleation affects the expression of the CB and c-Fos in the LGN complex. It is indicated that these may play an important role in the neuronal degeneration and neuroplasticity of the subvisual system in rats.

Wallerian Degeneration in the Optic Nerve of the Rabbit

Progressive anterograde axonal degeneration is known to follow after transection of the axon from the soma, which to some extent correlates with the passage of time after the lesion. However, the minimum time required for such changes to begin remains unresolved. In this study, 20 young adult rabbits of either sex underwent experimental monocular enucleation (left eye) under general anaesthesia. Left optic nerves from such animals were treated as experimental and those from either side of non-operated animals served as controls. Animals were sacrificed postoperatively at periods ranging from 12 h to 3 months. Brains were fixed with 10% formalin and Karnovsky fixatives by an intracardiac perfusion method. Light microscopy of 8-µm paraffin sections and 0.5-µm araldite sections from the optic nerves did not reveal any changes at 12 h. At 24 h, focal minute cavities appeared across the optic nerves. Those nerves from late postoperative stages revealed such cavities with increasing dimensions, disarray of fascicular organization, fragmentation, ovoid formation and finally dissolution of the myelin sheaths. There was an appreciable increase in the number, size and aggregation of glia cells. The debris of degeneration remained prominent even 3 months after enucleation. Electron microscopy revealed splitting of myelin, intramyelinic and periaxonal oedema and occurrence of amorphous and electron-dense materials in the degenerating nerve fibres. It was concluded that while the optic nerve showed degenerative changes as early as 24 h after enucleation, debris of degeneration was only partly removed even after 3 months.

Microarray analysis of developmental plasticity in monkey primary visual cortex.

We performed microarray gene expression analyses on the visual cortex of Old-World monkeys (Cercopithicus aethiops) in an effort to identify transcripts associated with developmental maturation and activity-driven changes during the visual critical period. Samples derived from normal animals and those subjected to monocular enucleation (ME) were hybridized to human Affymetrix HG-U95Av2 oligonucleotide microarrays (N = 12) and the results were independently validated by real-time quantitative RT-PCR. To identify genes exhibiting significant expression differences among our samples, the microarray hybridization data were processed with two software packages that use different analytical models (Affymetrix MicroArray Suite 5.0, dChip 1.2). We identified 108 transcripts within diverse functional categories that differed in their visual cortical expression at the height of the critical period when compared to adults. The expression levels of four transcripts were also globally modulated following ME during the critical period. These transcripts are particularly sensitive to ME during the critical period but are not significantly modulated in ME adults. Three of the ME-driven genes (NGFI-B, egr3, NARP) are known immediate-early genes (IEG) while the other (DUSP6) is a phosphatase that can regulate IEG expression. The putative biological significance of the ME-driven and developmentally regulated genes is discussed with respect to the critical period for activity-dependent visual cortical neuroplasticity.

Monocular enucleation induces nuclear localization of calcium/calmodulin-dependent protein kinase IV in cortical interneurons of adult monkey area V1.

Elevation of intracellular Ca2+ levels activates calcium/calmodulin-dependent protein kinase (CaMK) IV, which in turn plays an important role in neuroprotection and neuroplasticity. The possibility that CaMKIV is similarly involved in neocortical tissue has not been examined previously, especially with regard to the plastic nature of ocular dominance features in the primary visual cortex (area V1). We addressed this question by way of monocular enucleation (ME) to disrupt sensory input and examine CaMKIV expression changes in monkey area V1. Immunohistochemical staining of area V1 in normal infants showed a nuclear presence of CaMKIV, which did not changed after ME. However, a striking set of layer- and time-dependent changes in nuclear CaMKIV expression was observed in adult area V1 after ME. A strong increase in nuclear CaMKIV levels was evident in cortical layers II/III and VI after 1 d of ME and in layer IVC after 5 d of ME. These specific laminar changes persisted after 30 d of ME and, most notably, showed a columnar profile in which CaMKIV expression was linked to open-eye columns. Real-time quantitative reverse transcription-PCR and Western blot analysis showed that total amounts of CaMKIV mRNA and protein remained unchanged after ME, suggesting that a nuclear translocation may occur from the cytoplasm. Finally, double-label immunohistochemical staining with a pyramidal cell marker (SMI-32) showed that CaMKIV was absent in this subtype, whereas coincidental expression with GABA, parvalbumin, and calretinin, but not calbindin, showed its clear presence in a subset of interneurons. We propose that CaMKIV activity within diverse groups of cortical interneurons may play an important role in adaptive plastic reorganization of adult neocortical tissue.

Adenosine A 1 and Benzodiazepine Receptors and Glucose Metabolism in the Visual Structures of Rats Monocularly Deprived by Enucleation or Eyelid Suture at a Sensitive Period

Purpose: To determine the changes in the adenosine A 1 and benzodiazepine receptor density and in glucose metabolism in the visual centers of the rat brain following monocular enucleation or eyelid suture on postnatal day 10 (PN10). Methods: Following monocular enucleation or eyelid suture on PN10 rats, the alterations in adenosine A 1 and benzodiazepine receptor density, and in glucose metabolism were evaluated in the superior colliculus (SC), the dorsal lateral geniculate body (DLG), and the visual cortex (VC) by ex vivo autoradiography with [ 11C]MPDX, [ 11C]flumazenil and [ 14C]2-deoxyglucose, respectively. Results: Enucleation reduced the [ 11C]MPDX binding in the SC and DLG, and enhanced the [ 11C]flumazenil binding in the SC. Eyelid suture reduced the [ 11C]flumazenil binding in the VC at day 20. [ 14C]2-deoxyglucose uptake was not decreased by enucleation in any region except in the SC and DLG at day 1, but was decreased by eyelid suture in the SC at days 20 and 55 and in the VC at day 55. Conclusions: The decrease in the presynaptic adenosine A 1 receptors in the SC following enucleation is coupled with an upregulation of postsynaptic benzodiazepine receptors. These neural reactions are completely different from those following eyelid suture. The development of neural architecture for visual functions is not completed at PN10 in rats.

Immunocytochemical localization of calretinin in the superficial layers of the cat superior colliculus.

We localized calretinin-immunoreactive (IR) fibers and cells in the superior colliculus (SC) of the cat and studied the distribution and effect of enucleation on the distribution of this protein. Calretinin was localized with antibody immunocytochemistry. A dense plexus of anti-calretinin-IR fibers was found within the upper part of the superficial gray layer. Almost all of the labeled fibers were small diameter fibers with few varicosities. Monocular enucleation produced an almost complete reduction of calretinin-IR fibers in the SC contralateral to the enucleation. Furthermore, many calretinin-IR cells appeared in the contralateral SC. The newly appeared cells had small- to medium-sized vertical fusiform, oval or round, or stellate cell bodies. Two-color immunofluorescence revealed that no cells in the superficial layers expressed both calretinin and GABA. Many retinal ganglion cells were labeled after injections of retrograde axonal transport horseradish peroxidase (HRP) in the superficial layers. However, no large cells were double-labeled with calretinin and HRP. More than 95% of the double-labeled cells were small cells (<15 microm). Based on the retinal ganglion cell size, we believe that the vast majority of calretinin-IR retinocollicular fibers in cat SC are small gamma type cells that have W type physiologies.

Changes of calretinin, calbindin D28K and parvalbumin-immunoreactive neurons in the superficial layers of the hamster superior colliculus following monocular enucleation

We studied the effects of monocular enucleation on the patterned distribution of calretinin-, calbindin D28K- and parvalbumin-immunoreactive (IR) neurons in the superficial layers of the hamster superior colliculus (SC). The calcium-binding proteins were localized using antibody immunocytochemistry. Almost complete depletion of the calretinin-IR fibers in the superficial layers of the contralateral SC was found following unilateral enucleation. Quantitative analysis showed that on the experimental side of the SC, an enormous number of calretinin-IR cells newly appeared (716%). On the experimental side of the SC, the number of parvalbumin-IR cells also increased (32%). By contrast, on the experimental side of the SC, the number of calbindin D28K-IR cells exhibited a reduction (43%). Two-color immunofluorescence revealed that none of the newly appeared calretinin-IR cells were labeled with antibodies to calbindin D28K or parvalbumin. The present results demonstrate that retinal projection may control the activity of the expression of these calcium-binding proteins in the hamster SC but in different manners. The results also show that the patterned change of calretinin and parvalbumin in the hamster SC is comparable with other animals, but the change of calbindin D28K is not identical.

Cross-modal plasticity after monocular enucleation of the adult rabbit.

The mature brain undergoes compensatory reorganization of the primary visual cortex (V1) in response to retinal lesions. This study demonstrates that V1 also supports cross-modal reorganization by observing an increase in tactile responses in V1 after monocular enucleation of the adult rabbit. The proportion of tactile-responsive V1 neurons increased from 0% to 31%, in an area of cortex equivalent to 40 degrees of visual space. Retrograde fiber-tracing analysis suggests that intracortical connections from association areas may underlie these novel responses. Cortical plasticity of this kind may be involved in recovery from sensory system damage and could provide an enhanced sense of touch to the blind.

Neuroreceptor Bindings and Synaptic Activity in Visual System of Monocularly Enucleated Rat

Purpose: To study the changes in the distribution of postsynaptic benzodiazepine (BDZ) and presynaptic adenosine A 1 (AA 1) receptors in the superior colliculus (SC) and visual cortex (VC) of rats following monocular enucleation. Methods: The right eyes of 6-week-old Long-Evans rats were enucleated and ex vivo autoradiography was performed on the SC and VC obtained at different times up to 8 weeks after the enucleation. [ 14C]deoxyglucose was used to detect glucose metabolism, and [ 11C]flumazenil and [1-methyl- 11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine ([ 11C]MPDX) were used to map BDZ and AA 1 receptors, respectively. The receptor-specific binding for 11C was determined, and 11C and 14C activities were evaluated separately in the same tissue by a double tracing method. Results: The uptake of [ 14C]deoxyglucose in the SC was depressed immediately after enucleation and gradually recovered. The binding of [ 11C]flumazenil to BDZ receptors in the contralateral SC was increased at week 2, and then returned to the pre-enucleation levels. The uptake of [ 11C]MPDX by the AA 1 receptors in the contralateral SC decreased by about 67% on day 5 after enucleation and remained low thereafter. In the contralateral VC, the uptake of [ 14C]deoxyglucose decreased immediately after the enucleation followed by a gradual recovery, whereas the uptake of [ 11C]flumazenil and [ 11C]MPDX was not altered. Conclusions: The axon degeneration related decrease of the AA 1 receptor density resulted in a transient up-regulation of postsynaptic BDZ receptor density in monocularly enucleated adult rats. These results suggest that these radioligands can be used to study the distribution of the postsynaptic BDZ and presynaptic AA 1 receptors in the visual system and can probably be applied to the human visual system for positron emission tomography.